Elsevier

Transplantation Proceedings

Volume 52, Issue 8, October 2020, Pages 2503-2506
Transplantation Proceedings

14th Congress of the Polish Transplantation Society–Part II
Liver transplantation
Higher Concentrations of Cyclosporine Metabolites in Liver Transplant Recipients With a History of Viral and Bacterial Infections

https://doi.org/10.1016/j.transproceed.2020.03.039Get rights and content

Highlights

  • Higher CsA metabolites were associated with viral infections after LTX.

  • Higher CsA metabolites were associated with bacterial infections after LTX.

  • We present CsA metabolites monitoring as an infection-prediction strategy.

Abstract

Background

Infection remains a serious clinical problem in liver transplant (LTX) recipients. A higher risk of infection is connected with immunosuppression therapy. The aim of the study was to assess the relationships between infections’ incidence and concentrations of cyclosporine (CsA) metabolites after LTX.

Methods

Forty-three liver transplant recipients receiving CsA were included in the study. With the use of liquid chromatography combined with tandem mass spectrometry, concentrations of CsA and its metabolites were measured: dihydroxylated cyclosporine metabolites (DiHCsA), trihydroxylated cyclosporine metabolites (TriHCsA), demethylcarboxylated cyclosporine metabolites (DemCarbCsA), AM1, AM9, and AM4N. The study protocol conformed with the Declaration of Helsinki.

Results

Patients with a history of Epstein-Barr virus (EBV) infection had higher DiHCsA, TriHCsA, DemCarbCsA, AM1/CsA, DiHCsA/CsA, TriHCsA/CsA i DemCarbCsA/CsA in comparison with group without such infection (P = .049, P = .037, P = .006, P = .018, P = .005, P = .027, and P = .026, respectively). LTX recipients with a history of all viral infections had higher DiHCsA, TriHCsA, DiHCsA/CsA, TriHCsA/CsA than patients without viral infections (P = .013, P = .021, P = .013, and P = .048, respectively). Multivariable analysis showed that AM1, DiHCsA, TriHCsA, DemCarbCsA, AM4N/CsA had positively influence on the incidence of all viral infections (β = 0.0302, P = .0328; β = 0.0699, P = .0453; β = 0.6781, P = .0382; β = 0.6767, P = .0414; and β = 0.8307, P = .0267, respectively). In multivariable analysis, patients with a history of all bacterial infections had higher AM1 and higher AM1/CsA in comparison with LTX recipients without such infections (β = 0.0118, P = .0279; and β = 0.0099, P = .036, respectively).

Conclusion

In liver transplant recipients with a history of viral or bacterial infections higher concentrations of CsA metabolites were found. Possibly CsA metabolites could be used to assess the risk of infection in patients after liver transplantation. It should be confirmed in further investigations.

Section snippets

Material and Methods

Blood samples were obtained from LTX recipients who gave their written informed consent to participate in this study. Forty-three stable patients following LTX were included in the study. The median age was 50.4 years, interquartile range (IQR) 31.8 to 59.1. The group included 22 male (51.2%) and 21 female (48.8%) subjects. The median post-transplant time was 107.4 months, IQR 48.7 to 162.1. 2 mL trough blood samples were collected into ethylenediamine tetraacetic acid–containing tubes during

Results

Patients’ characteristics and concentrations of CsA and its metabolites are presented in Table 1. Liver recipients with a history of EBV infections had higher DiHCsA, TriHCsA, DemCarbCsA, AM1/CsA, DiHCsA/CsA, and TriHCsA/CsA i DemCarbCsA/CsA in comparison with subgroup without such infection (498.396 ± 591.829 vs 53.042 ± 44.923, P = .049; 33.368 ± 41.548 vs 1.627 ± 2.558, P = .037; 28.222 ± 34.506 vs 0.482 ± 1.007, P = .006; 639.605 ± 41.797 vs 384.162 ± 120.946, P = .018, 654.547 ± 716.736 vs

Discussion

Infections are often the cause of morbidity and mortality in LTX recipients. Among 2761 solid organ transplant recipients (including 577 LTX recipients), 1520 patients (55%) suffered 3520 infections during the first year post-transplantation [5]. Authors underline that, in the whole group, the most common complication was bacterial infection (63%). However, in LTX patients, EBV infection also seems to be a serious problem. It can lead to post-transplant lymphoproliferative disorder (PTLD),

Conclusions

In conclusion, in LTX recipients with a history of viral or bacterial infections, higher concentrations of CsA metabolites were observed. It is possible that the quantification of CsA metabolites could be a part of therapeutic drug monitoring strategy and could be used to assess the risk of infection in patients after LTX. This hypothesis should be confirmed in further investigations.

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This work was supported by Polish National Science Centre, Poland (grant no. 2013/09/B/NZ2/00275) and Polish National Centre of Research and Development, Poland (grant no. NR13014410).

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